The Cystic Fibrosis Research Center (CFRC) at the University of Pittsburgh is comprised of ~50 faculty members from ten departments, providing research strengths from basic and clinical investigators. It garners more than $13 M/yr in extramural grants and contracts to support its CF research efforts. They are focused on three major scientific themes. The Center has a strong basic and pre-clinical science component that addresses the Cell and Molecular Biology of CF and CFTR, and it is supported by NIH, NSF and Cystic Fibrosis Foundation (CFF) grants. Investigators in this group make extensive use of differentiated, primary human bronchial epithelia (HBE), and more recently human nasal epithelia (HNE), to define important steps in CFTR trafficking, airway liquid transport and mucociliary clearance. These studies are directed at elucidating the functional properties of wild type CFTR in relation to its more or less common disease mutants, as well as CFTR's associated transporters, including ENaC and SLC26A9. P30 investigators are identifying their impact on ER protein biogenesis and quality control, post-ER trafficking and their impact on the regulation of airway surface liquid volume and composition, studies that are directed to facilitate therapeutics development. Technical expertise and HBE having specific mutations are being provided to academic and industrial partners for the development of drugs that are currently available to patients or are in clinical evaluations. The Infection and Immunity component of the Center focuses on airway bacterial and viral infections, their interactions, and mechanisms of innate and adaptive immunity, using HBEs and animal models. These studies aim to improve our understanding of the inflammatory response in CF disease pathogenesis, define biomarkers and outcome measures to improve clinical trials, and identify targets for anti-inflammatory therapy, often through industrial interactions. Third, the Translational/Clinical Studies component translates pre-clinical findings into new therapeutic approaches. It develops and evaluates methods to improve and standardize airway drug delivery, in vivo isotopic clearance and liquid absorption assays, and test therapeutics that target the core defect in CF. The proposed CF Research and Translation Core Center (P30) is directed by Dr. Raymond Frizzell with Drs. Jay Kolls and Joseph Pilewski serving as Associate Directors. The Center is comprised of three scientific cores that support its large research base: Human Airway Cells and Assays (Drs. Frizzell and Pilewski, PIs), Translational/Clinical Studies (Drs. Pilewski and Kolls, PIs), and Imaging (Dr. Simon Watkins, PI). In the last grant period, several new assays have been developed by core associated investigators. The Core Center operates a Pilot and Feasibility Program to initiate new investigators into CF research and to facilitate the pursuit of new important ideas by established scientists and clinicians. The Center emphasizes the translation of basic knowledge into applied therapeutics.